Trials@uspto.gov
`571-272-7822
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`Paper # 75
`Entered: August 8, 2023
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`________________
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`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________
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`MYLAN PHARMACEUTICALS, INC., MSN LABORATORIES
`PRIVATE LTD. and MSN PHARMACEUTICALS INC.,
`Petitioners,
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`v.
`
`BAUSCH HEALTH IRELAND LIMITED,
`Patent Owner.
`________________
`
`IPR2022-007221
`Patent 7,041,786 B2
`________________
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`Held: June 14, 2023
`________________
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`Before TINA E. HULSE, CYNTHIA M. HARDMAN, and
`MICHAEL A. VALEK, Administrative Patent Judges.
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`1 IPR2023-00016 has been joined with this proceeding.
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`571-272-7822
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`Paper # 75
`Entered: August 8, 2023
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`________________
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________
`
`MYLAN PHARMACEUTICALS, INC., MSN LABORATORIES
`PRIVATE LTD. and MSN PHARMACEUTICALS INC.,
`Petitioners,
`
`v.
`
`BAUSCH HEALTH IRELAND LIMITED,
`Patent Owner.
`________________
`
`IPR2022-007221
`Patent 7,041,786 B2
`________________
`
`Held: June 14, 2023
`________________
`
`
`
`
`Before TINA E. HULSE, CYNTHIA M. HARDMAN, and
`MICHAEL A. VALEK, Administrative Patent Judges.
`
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`
`
`1 IPR2023-00016 has been joined with this proceeding.
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`
`IPR2022-00722
`Patent 7,041,786 B2
`
`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER:
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`
`Jad Mills
`Richard Torczon
`Tasha Thomas
`Wilson Sonsini Goodrich & Rosati
`701 5th Ave #5100
`Seattle, WA 98104
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`Andrew Larsen
`Melissa Hayworth
`Merchant & Gould P.C.
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`
`ON BEHALF OF THE PATENT OWNER:
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`
`Justin Hasford
`Kassandra Officer
`Finnegan, Henderson, Farbow, Garrett & Dunner LLP
`901 New York Ave, NW
`Washington, DC 20001
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`The above-entitled matter came on for hearing on Wednesday
`June 14, 2023, commencing at 2:00 p.m. ET, via video teleconference.
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`Patent 7,041,786 B2
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`P R O C E E D I N G S
`JUDGE VALEK: I'm Judge Valek, and with me on the panel are
`Judges Hulse and Hardman. This is the oral hearing for IPR2022-00722,
`and IPR2023-00016, which has been joined with this proceeding. The
`Petitioners are Mylan Pharmaceuticals, MSN Laboratories, and MSN
`Pharmaceuticals. The Patent Owner is Bausch Health Ireland. This hearing
`is open to the public, and a transcript will be made of record. Counsel for
`Petitioner, would you please identify who is present for the Petitioner and
`who will be speaking on its behalf?
` MR. MILLS: Yes, this is Jad Mills present for the Petitioner.
`I'm lead counsel. I will be speaking on behalf of the Petitioner, Mylan, and
`with me in the conference room I have Rick Torczon, and Tasha Thomas.
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`JUDGE VALEK: Thank you. Counsel for Patent Owner,
`would you please identify who is present for Patent Owner and who will be
`speaking on its behalf?
` MR. HASFORD: Yes, Your Honor. It's Justin Hasford here of
`Finnegan, on behalf of Patent Owner. I'm also joined by my partner,
`Kassandra Officer of Finnegan for the Patent Owner. We plan to divide our
`argument. At the present time we plan to have 50 minutes have been
`reserved, 10 minutes for rebuttal, and I plan to speak for roughly the first 40
`minutes, and she plans to speak for the next 10 on objective indicia.
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`JUDGE VALEK: Okay. Now I know that they're in an
`understudy role, but do we have any counsel for MSN on the line?
` MR. LARSEN: Yes, this is Andrew Larsen. I'm lead counsel
`for Joint Petitioner, MSN. We're the joined Petitioners. I believe with me
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`IPR2022-00722
`Patent 7,041,786 B2
`listening in is our back up counsel, Melissa Hayworth, as well.
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`JUDGE VALEK: Okay. Thank you, Mr. Larsen. As indicated
`in our trial order, each side will have the 60 minutes to present its case.
`Petitioner will present its case first, followed by the Patent Owner. Counsel
`for Petitioner, would you please -- would you like to reserve any time for
`rebuttal?
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` MR. MILLS: Yes. We would like to reserve 25 minutes for
`rebuttal.
`JUDGE VALEK: Counsel for Patent Owner, would you like to
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`reserve any of your time to follow Petitioner's rebuttal?
` MR. HASFORD: Yes, Your Honor, we plan to reserve 10
`minutes.
`JUDGE VALEK: Okay. Before we begin the parties'
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`presentations, I'd like to go over a few things. First, this is an all-video
`remote hearing. Our primary concern is your right to be heard. If at any
`time during the hearing you encounter technical or other difficulties that you
`feel undermine your ability to represent your client, please let us know
`immediately. To help with the transcript, we ask that you identify yourself
`when you speak, and mute your microphone when not speaking. Also, let's
`all do our best to remember to pause and try to avoid talking over each other.
`The panel has access to the entire record, as well as the demonstratives. If
`you wish, you can share your screen so that you can control the particular
`demonstratives on display.
`But please make sure that you orally announce the demonstrative
`number or the particular page of the paper or exhibit you're referring to so
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`IPR2022-00722
`Patent 7,041,786 B2
`that the record is actually on the transcript. In addition to the issues that are
`presented by the Petition, each side has filed a motion to exclude certain
`exhibits and testimony from this trial. Those motions are Papers 54 and 55.
`We expect to rule on those motions in our final written decision. There are
`no other motions pending, so you're free to allocate your time today as you
`choose, but it is the panel's expectation that the arguments will focus
`primarily on the grounds in the Petition. Does either side have any questions
`before we begin?
` MR. MILLS: No, Your Honor.
` MR. HASFORD: None from us, Your Honor.
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`JUDGE VALEK: Okay. Mr. Mills, you may begin Petitioner's
`argument.
` MR. MILLS: Thank you, Your Honors. This is a
`straightforward case of obviousness. There was good reason to look to the
`body's natural laxative peptide, which is uroguanylin, and which was
`designed through millions of years of evolution to add fluid to the intestines
`naturally and gently. And to make one conservative substitution, it was
`specifically suggested by the uroguanylin consensus sequence disclosed in
`the prior art. Having established good reason to make the claimed peptide,
`there is no dispute that there was a reasonable expectation of success for
`making the claimed peptide.
`Looking now at slide 2. In the face of the straightforward case,
`Bausch peppers the record with misdirected arguments, but each of them is
`riddled with errors. As just a couple of examples, I want to talk with you a
`little bit later today about the mischaracterization of the Hamra and Li
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`IPR2022-00722
`Patent 7,041,786 B2
`references, and even of Bausch's own alleged unexpected results evidence.
`This patent and the thicket of following patents that Bausch obtained after it
`were issued in error and continue to exist only because Bausch is very
`skilled at telling tales that have no basis in reality.
`But before we get to that, I want to spend at least a little bit more
`time talking about the prima facie case. Please turn to slide 10. Slide 10
`shows us the claims of the challenge patent. Each of these claims is directed
`to a peptide with an amino acid sequence, that's Sequence ID No. 20. Please
`turn to slide 11. The only difference between the claimed uroguanylin
`peptide and the prior art uroguanylin peptide is that single substitution
`replacing the Asp at position three, with the Glu residue at position three.
`And the only difference between these two residues is the presence of an
`additional methylene unit in the slide chain. Please turn to slide 13. Slide
`13 provides a summary of four reasons to make a synthetic uroguanylin
`analogue. Why make a synthetic uroguanylin analogue? There are many
`reasons, but the simplest is that the prior art tells us to.
`First, uroguanylin was the body's natural laxative. It was useful for
`controlling intestinal absorption, and even for displacing the ST in teradoxin.
`Currie tells us all about it. Second, it was sufficiently stable to be
`administered orally. They had already done that in the prior art.
`Uroguanylin made it all the way to the stomach, and uroguanylin caused
`intestinal fluid secretion in the intestines just as intended. Third,
`uroguanylin had enhanced potency as compared to guanylin at the relevant
`intestinal pH for the tissue designed by the body to add fluid into the
`intestines.
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`Patent 7,041,786 B2
`Because of its acidic residues, either an Asp or a Glu, at positions
`two and three. And fourth, uroguanylin lacked the toxic potency of
`enterotoxin. Unlike uroguanylin, which was designed as the body's natural
`gentle way to increase intestinal fluid, enterotoxin developed to fulfill the
`goals of packages like E. coli. They want to cause severe diarrhea to release
`the bacteria to find a new host. This is what enterotoxins were designed to
`do.
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`Currie was well aware of guanylin, uroguanylin and enterotoxin,
`and how each of them was designed. Currie concluded that the
`physiological characteristics of uroguanylin, that the uroguanylin was,
`"important to medical science in the study of regulators of guanylate
`cyclase." (INDISCERNIBLE) can be identified as lead more explicitly than
`human uroguanylin. Please turn to slide 14. Slide 14 provides a summary
`of six reasons a person of ordinary skill in the art would have made Glu3 to
`the uroguanylin. Each of these reasons is discussed in detail on the Petition,
`the reply, and the Peterson declarations. And in a moment, I'd like to
`discuss at least some of them in greater detail.
`But first, I want to at least touch on reasonable expectation of
`success. Please turn to slide 15. As shown in slide 15, there's no genuine
`dispute that a person of ordinary skill in the art had a reasonable expectation
`of success from making Glu3 Human Uroguanylin. Peptide synthesis was
`quite routine by this time. The Currie reference specifically teaches solution
`and solid-phase synthesis should be used to make synthetic uroguanylins.
`As the Federal Circuit held in Intelligent Bio-Systems, reasonable
`expectation of success is required only for what is claimed. If it is not
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`IPR2022-00722
`Patent 7,041,786 B2
`recited in the claim, "it is of no moment." The Patent Owner has never
`argued that a person of ordinary skill in the art lacked a reasonable
`expectation of success from making the claimed peptide, and in fact, its
`expert has conceded the issue. Please turn to slide 16.
`As shown in slide 16, Patent Owner's chemistry expert, Dr. Davies,
`conceded during his deposition that, "in terms of the chemistry, they would
`have been able to do it," meaning to make the peptide. The dispute raised
`by Patent Owner's experts is about whether making Glu 3 human
`uroguanylin would have been a goal a person of ordinary skill in the art
`would have wanted to achieve. As I previewed at the beginning of my
`presentation, and as I will now address in greater depth, of course it would
`have been (PHONETIC).
`Please turn to slide 23. Slide 23 shows how Li aligned the
`homologous uroguanylin sequences to show the uroguanylin consensuses.
`We specifically called out positions 2 and 3 indicated by the stippled
`arrowheads, the gray arrowheads on the lefthand side, as requiring an amino
`acid acidic residue, either an Asp or a Glu to maintain uroguanylin's
`enhanced cogency in the target tissue of interest.
`Li explains that it is of, "particular interest that the residues at
`positions 2 and 3 are acidic in the consensus sequence of uroguanylin but are
`basic or uncharged in guanylin. By following the consensus sequence for
`uroguanylin, of having acidic residues at positions 2 and 3, Li concludes,
`"we would expect," Li says, that the GC-C affinity of rat uroguanylin would
`be comparable to that of opossum or human uroguanylin, and Li explains
`that those response curves using the synthetic rat peptide would be required
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`IPR2022-00722
`Patent 7,041,786 B2
`to test this expectation directly. Please turn to slide 24.
`Slide 24 shows that there are only two acidic or proteogenomic,
`which means natural, amino acid residues, Asp and Glu. There's really only
`one choice for positions 2 and 3 of human uroguanylin. To make a synthetic
`uroguanylin analogue, substituting Glu in place of Asp was the obvious
`choice. Li's teaching that the Glu 3 substitution was consistent with the
`uroguanylin consensus sequence is supported by additional references.
`Please turn to slide 25. Slide 25 provides a quote from Hamra 1997. Hamra
`confirms that there is a consensus sequence for uroguanylin, and that it
`includes either an Asp or a Glu at positions 2 and 3 of the peptide. "All
`uroguanylin peptides have an aspartate or glutamate residue at these
`positions." This is, "required for the increased binding affinities," and
`further, "enhanced potency of uroguanylin for activation of the GC-C
`receptors under acidic condition." The uroguanylin consensus sequence at
`positions 2 and 3 limited the substitution choices to replace an Asp with Glu
`to retain uroguanylin's enhanced potency under acidic conditions.
`In our slides 4 through 7, we discuss that these are the same acidic
`conditions that are especially relevant in the small intestines, which are the
`primary organ of the GI tract that the body designed to add fluid to the
`intestinal lumen, in contrast to the large intestines whose primary purpose is
`to remove fluid from the intestinal lumen. Millions of years of evolution
`provided clear instructions for making a synthetic uroguanylin analogue to
`increase fluid in the intestinal lumen. Replace the Asp at position 3 with
`Glu.
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`JUDGE VALEK: Counsel, this is Judge Valek. I have a
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`Patent 7,041,786 B2
`question for you. I think that I understand your argument that if you were
`going to make a change to the residue at the position 3, you'd want to use
`another acidic residue and there's only one. But what is the evidence that
`you have that one in the skill of the art would actually want to make a
`change in that position? If it's not broke, why fix it, is the question I'm
`asking you.
` MR. MILLS: Well, first I'd like to turn to slide 19, and in
`particular at the bottom in our cites we have a see also cite to the Currie
`reference at page three, where it says, "The novel peptide in the invention
`can be prepared by known solution and solid phase peptide synthesis
`method." So, number one, the Currie reference is telling us that we're not
`going to be isolating the uroguanylin, which is something that can be done
`and was being done, but that it is a preferable thing to be synthesizing rather
`than isolating. One of the rationales for the substitution, looking now at
`slide 14, one of the rationales is that when you're doing a synthesis of human
`uroguanylin, there is synthetic Albom which is called aspartimide formation.
`And that this specific substitution, standing head and shoulders above other
`potential substitutions, eliminates the amino acid pairs that cause the
`aspartimide formation. I'd look at slide 11 just to illustrate this.
`When you look at the sequence here, the problem in the human
`uroguanylin, which is in the bottom, is that you have -- in positions 2
`through 4, you have two pairs, Asp 2 to the left of Asp 3, and then Asp 3 to
`the left of Cys 4. Each of those leads to unwanted aspartamide formation,
`even when protecting groups are used, and there are some additional
`protecting groups that could be used, but they work in some situations and
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`IPR2022-00722
`Patent 7,041,786 B2
`not others, and they are extremely burdensome. This single substitution
`solves this problem, and it gives you a peptide that follows the natural
`pathway without the synthetic problem.
`The other thing I'd like to point to on slide 12, so here's a little bit
`of case law from In re Dillon and from the BMS case from the Federal
`Circuit. So when there is a compound that's not in the art, a peptide that's
`not in the art to have a function that's useful, it's prima facie obvious to make
`close relatives to the homologs, analogs, and isomers. And that's the In re
`Dillon case, it's an ongoing decision by the Federal Circuit. And it's also not
`required that the analogue be expected to have superior properties. That's an
`argument that was argued a lot from the Patent Owner saying that they think
`we haven't proven that the properties will be clearly superior. But that's not
`a prerequisite.
`Here in the BMS case, the Federal Circuit is telling us that if there
`is a claimed prior art compound that has a sufficiently close relationship but
`there's an expectation, in light of the totality of the prior art, that the new
`compound will have similar properties to the old and it is obvious. This
`also goes to the motivation and the scope in the field. The Patent Owner
`essentially imagines in the grass under the definition --
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`JUDGE VALEK: Counsel, I want to interrupt you before you
`move on. The Dillon case that you cite, the presumption that you have up on
`your slide 12, has that presumption been applied by the Federal Circuit
`outside of an ex parte context?
` MR. MILLS: I don't have that specific case to give you, Your
`Honor, right now. Sorry, did I answer your question? The point that I
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`wanted to make about the Patent Owner's conception of a person of ordinary
`skill in the art, they conceive of that person of ordinary skill in the art as
`essentially a protein chemist, one who is reluctant to make a peptide at any
`point unless they've resolved every question about essentially how it's going
`to be commercialized and so forth. And that's really inconsistent with what
`the literature tells us about the state of the art.
`When you look at the literature, the literature indicates a person of
`ordinary skill in the art is very eager to synthesize peptides, the burden for
`making a peptide is extremely low. It's something that's not difficult to do,
`and because of that, this is not an insurmountable barrier that prevents a
`person of ordinary skill in the art from wanting to make a peptide. It's
`something that when you have this very favorable analogue -- sorry, this
`very favorable peptide, and you know that you can make a synthetic version
`of it -- it's not the original, it's not the one in nature, but it's so close to it that
`it's likely to retain all of its favorable properties, and even improve upon
`those properties that a person of ordinary skill in the art has motivation and
`wants to make that. If I can, I'd like to look at slide 26 now.
`So this is testimony from Dr. Peterson where he said, because of
`the chemical and physical properties of the amino acids involved in this
`conservative substitution, that this provided a strong indication to skilled
`artisans that the particular substitution was both biologically acceptable and
`that it would retain or even improve the functionality. Looking at slide 27,
`it's important to understand also that there was a functional overlap that was
`understood between a human and the rat receptors that were being targeted.
`Currie tells us that human uroguanylin activated the target receptor
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`in rats, and it tells us that the rat uroguanylin activated the target receptor in
`human cells. Because the obviousness of the Glu 3 uroguanylin is so plain,
`the Patent Owner has variously argued that a person of ordinary skill in the
`art would not have made the peptide because they say it would have
`decreased activity. Where they have contradictorily argued that a person of
`ordinary skill in the art would have deliberately decreased its activity by
`making it more like guanylin to more exclusively target the Glu.
`There's not enough time to go through all of the reasons that each
`of these arguments are incorrect. But in the interest of time, I'd like to
`briefly discuss their misinterpretations of the Hamra and Li references.
`Please turn to slide 30. Slide 30 shows Figure 1 of Exhibit 1019. This is
`Hamra 1996. The parties agreed that uroguanylin evolved to have enhanced
`potency in the acidic mucosa of the intestines, and that guanylin did not.
`Uroguanylin's response is greatest at a pH of 5, as compared to itself. In
`guanylin's activity is highest at a pH of 8, as compared to the cell.
`It's important to look at what the Y axis tells us. It's not comparing
`the absolute activity levels between the two peptides. It's telling us at each
`data point the percentage of each peptide’s maximum capacity for that
`particular peptide at that particular pH. Hamra suggests that uroguanylin is
`either inactive or less active than guanylin at a neutral or alkaline pH, such
`as 7.5, or 8.0, and argues that there is therefore a teaching away from the Glu
`3 substitution. But Bausch is wrong.
`Figure 1 tells us that uroguanylin has a very high activity
`throughout the pH range. It's about 50 percent of its capacity until
`approximately pH 7. And even above that remains above 40 percent of its
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`Patent 7,041,786 B2
`own capacity. In contrast, guanylin starts off near zero percent of its
`maximum capacity. And its activity only becomes okay at the higher pHs.
`Look at the caption. You will see that there is no point at which uroguanylin
`is not at least 70 percent higher than guanylin, and that's at the pH of 8. At a
`pH of 5, uroguanylin is more than 43-fold higher than guanylin. Bausch's
`interpretation of Hamra is clearly erroneous, and this is just one example.
`Please turn to slide 34.
`Slide 34 shows us Li Figure 3. Bausch relies on Li Figure 3 and
`relies on it to make an apples to oranges comparison. But Li is not showing
`you what Bausch claims it is showing you. Bausch argues that the bar graph
`labeled uroguanylin shows you that the activity of synthetic opossum
`uroguanylin is something 20 times higher than the activity of the extracted
`rat uroguanylin in fraction 16 and argues that this is a teaching away.
`But Li was not making any activity comparison across peptides. It
`was comparing each peptide to itself before and after protease incubation.
`Because this experiment was not designed to compare peptides, there's no
`indication that the peptide concentrations were the same across the different
`peptides because each peptide has a completely different origin. Some were
`HPLC standards obtained from different labs, and others were extracted
`from the tissue by Li. Bausch's assumption that Li permits a cross peptide
`comparison is now only in its own imagination. And its misunderstanding
`of Li infects the declarations of both Drs. Davies and Waldman.
`Dr. Davies, if you read his deposition transcript, which I encourage
`you to do, he is very confused about what Li Figure 3 is about. We spent
`quite a bit of time studying it together before he came to understand what it
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`IPR2022-00722
`Patent 7,041,786 B2
`was really talking about. Their adoption of this erroneous argument
`illustrates that they accepted Bausch's erroneous arguments without analysis
`or independent thought. Li's misguided arguments, whether they come the
`mouth of the experts or the attorneys, should be soundly rejected. Bausch's
`misapprehension of the evidence does not end with the prior art. Bausch's
`interpretation of its alleged unexpected results is also filled with errors.
`
`JUDGE VALEK: Mr. Mills, while we're on the subject of Li
`Figure 3, is there any evidence in the record that suggests that rat
`uroguanylin has greater potency or binding affinity than human
`uroguanylin?
` MR. MILLS: As I see it, the evidence tells us that they have
`comparable activity. That's the expectation that Li provided --
`
`JUDGE VALEK: But nothing suggests it would have greater
`activity? That's the question I'm asking you.
` MR. MILLS: Yes, so I don't believe there's anything in the
`record saying that either opossum, or rat, or human uroguanylin has a clear
`potency benefit as compared the others in these assays. But when evaluating
`that question, it's important to keep in mind the constraints on these type of
`assays. So this cycle of GMP assays that are performed is your biological
`assays. Dr. Peterson explained that for these types of assays, you really see
`a high degree of variability. There's a variety of reasons for that. Anyone
`that's done a biological assay knows that you get that type of variability.
`Some of the reasons are just the ability to precisely put in the amount of a
`protein receptor into each well and have it be identical, to put the peptide in.
`And you see a lot of variability. That's one of the things I want to talk about.
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`IPR2022-00722
`Patent 7,041,786 B2
`So, Dr. Peterson explained that for these type of assays, until you're seeing a
`difference of more than two-fold or three-fold, you can't even begin to come
`to a conclusion that a nominal difference that you're seeing is an actual
`difference. It actually represents a difference between the peptides. Does
`that answer your question?
`
`JUDGE VALEK: Yes, it answers my question about Li Figure
`
`3.
`
` MR. MILLS: Okay. I'd like to turn to slide 48. Bausch argues
`that there are four categories of unexpected results, but they really boil down
`to two. And the first category for three of their different categories they
`point to, they're all cyclic GMP data. And for the reasons that we just
`discussed, and I'll talk about in greater depth, the difference is that they point
`to are smaller than this type of assay it has the capacity to differentiate in
`between. So, they say that they're looking at affinity as an unexpected
`result, but really their only argument for the relevance of that affinity is to
`the extent it translates into activity or potency. So, in other words, the cyclic
`GMP assets. They also took about heat stability, but that once again it's a
`cyclic GMP study that they're looking at where they're pointing to a nominal
`difference that in reality is not significant, it's not real, it's not material.
`The other category that they point to is they talk about topo
`isomeric interconversion. And when they're doing this, it's important to
`keep in mind the context of what it is that they are pointing to. So, in the
`heat stability studies and in the topo isomeric conversion study, they're
`subjecting the peptides to very extreme conditions. For the heat stability
`they are boiling the peptides for 90 minutes, an hour and a half. They're
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`IPR2022-00722
`Patent 7,041,786 B2
`essentially making stew out of the peptides. And for their topo isomeric
`interconversion experiments, they are cooking the peptides in acid at a pH of
`3, or a pH of 4.5 for 16 hours, or 24 hours. And then they're trying to see if
`they can see any result.
`But all of the nominal results that they show in each of their
`studies, they depend on several critical errors. So among these, Bausch
`assumes that these experiments have a greater precision for distinguishing
`results than they can possibly get. And in the process of making that
`assumption they think that there are differences that these nominal
`differences they fail to demonstrate every significant, real, and material
`difference. Another problem is that they arrange the date in a manner to
`give a false impression that there is a significant or material difference when
`the data indicate that the opposite is true. Please turn to slide 50.
`So, I mention that most of their unexpected results arguments
`come down to cyclic GMP experiments. And they point specifically to
`Table 4, it's on the righthand side of this slide 50. They point to that, and
`they say that there is a 56 percent difference in the cyclic GMP value
`reported for the prior art uroguanylin, which is Sequence ID number 1, or
`SP301 in Table 4. And the value reported for the claim’s peptide, which is
`Sequence ID number 20, or SP304, here in Figure 4. So they point to this 56
`percent difference. This Table 4 is the data that they chose to publish in
`their patent.
`Table 1 is the material that they held back as confidential until last
`week. You can see from the color coding that most of the numbers match.
`They appear to come from Table 1. There's an exception where they use a
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`IPR2022-00722
`Patent 7,041,786 B2
`different concentration for SP304, than the others, but that those numbers are
`fairly close. But the key is if you look at SP302. It's one of the analogues
`that they made and that they looked it. And in Table 1 when they're running
`this experiment, they get a value of 185. And then they report that value in
`Table 4 as 225. So it's the same experiment, the same peptide, the same
`concentration, the same pH, but they get numbers that nominally look very
`different. So the question is, are those values really different, and why
`would they be?
`Please turn to slide 51. Here on slide 51, you can see Dr. Davies's
`testimony. This is Patent Owner's catalyst. He said that the value reported
`in Tables 1 and 4 for the same peptide and the same experiment differ by 40
`percent. But he testified that this magnitude of a difference doesn't mean
`anything. He said it's just a different way of processing the number. Keep
`in mind, the expected difference in activity -- the alleged unexpected
`increase in activity that Bausch relies on, is a very similar percentage of 56
`percent. Bausch's unexpected results numbers cannot be interpreted to
`demonstrate any significant, real, or material difference from the prior art,
`much less a difference in time.
`
`JUDGE VALEK: Mr. Mills, this is Judge Valek again. The
`quote that you have from Dr. Davies, is he testifying about the data that's on
`your slide 50 that comes -- I guess part of it comes from the patent and part
`of it comes from one of the reports to FDA. Is he testifying about that data
`specifically, or data from some other source?
` MR. MILLS: Yes. He was showing this discrepancy. He was
`asked specifically about this discrepancy. And seeing this discrepancy,
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`IPR2022-00722
`Patent 7,041,786 B2
`excuse me, seeing this discrepancy, he thought that the difference was 40
`percent, and he said a 40 percent difference doesn't mean anything. He
`testified specifically about this difference.
`Please turn to slide 52. So, slide 52 shows just how lacking in
`credibility these Bausch's unexpected results arguments are. Tables 2 and 3
`are additional Bausch tables that Bausch submitted to FDA, but did not
`publish in its patent, and which it held back as confidential until last week.
`In here, when Bausch compared the prior art uroguanylin with the claimed
`uroguanylin, the alleged 56 percent advantage that they had published in
`their patent completely vanishes. In fact, now, in both tables, Bausch's data
`shows that uroguanylin is more active than the claimed uroguanylin. In fact
`it's 20 percent more active. So the 56 percent asserted advantage disappears
`completely. You have a 20 percent advantage going in the other direction.
`That's a very w
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